Our project aims at establishing the genetic basis of antigenicity expressed by Class I glycoproteins of the major histocompatibility complex of the mouse (H-2). We will isolate H-2 genes as functional entities. Functional assays for the cloned genes expression will be used to identify the gene product which appears, subsequent to transfection, on the surface of recipient cell lines. Cell mediated cytototxicity assays will be used to assign the cloned genes to their corresponding H-2 subregions. At the DNA level, the differences between alleles and genes of the K, D and L subregions of H-2 will be investigated. We will construct in vitro mutations at various specific positions of the cloned genes and on the basis of the functional properties of the mutated gene products we will determine which regions of H-2 are directly involved in the generation of antigenic polymorphism. We will try to establish in a series of experiments involving wild type and in vitro mutant alleles, correlations between the alloantigenicity of the H-2 molecules and their ability to focus the function of antigen-specific MHC restricted cytotoxic T cells. Our proposal involves methodology and theoretical approaches belonging to: cellular immunology, molecular biology, and immunogenetics. Results to be obtained by carrying out the proposed experiments could be relevant to: transplantation biology, tumor immunology and pathogeny of MCH linked diseases.